In the process of seeking better methods of protecting myocardial function during open heart operations, we are attempting to define the pathophysiology of myocardial deterioration during global ischemia while on cardiopulmonary bypass. Employing the isolated cross perfused dog heart as an experimental model, we have correlated physiologic and biochemical data obtained during graded ischemic injuries under normothermic and hypothermic conditions. We have recorded parameters of systolic function, diastolic compliance and wall thickness and correlated them with biochemical measurements including tissue glycogen, CPK, water content, ATP, creatine phosphate and calcium. In examining hypothermia as a method of myocardial protection, we have found that preservation of systolic and diastolic performance is most closely correlated with the prevention of calcium deposition during reperfusion after ischemia. Similarly, the use of hyperkalemic normothermic solutions as a means of protection against global ischemia is also associated with the prevention of calcium deposition during reperfusion. We are currently pursuing investigations into the relationship among ATP, creatine phosphate, and calcium metabolism during ischemia and during interventions designed to prevent its ill effects on myocardial tissue.